伊贝沙坦和培垛普利对左心室肥大时心肌连接蛋白43、结蛋白与肌钙蛋白T表达的实验研究

Effects of irbesartan and perindopril on the myocardial expression of connexin 43, desmin and cardiac troponin T in rat cardiac hypertrophy induced by pressure overload

目的:探讨左室肥大时血管紧张素Ⅱ受体Ⅰ型拮抗剂伊贝沙坦和血管紧张素转换酶抑制剂培垛普利对心肌连接蛋白43(CX43)、结蛋白与肌钙蛋白T(cTnT)表达的影响。方法:分假手术组、SD大鼠腹主动脉部分结扎的手术组及腹主动脉部分结扎的处理组即伊贝沙坦组(20mg·kg-1·d-1ig)、培垛普利组(2mg·kg-1·d-1ig)、两药联用组(伊贝沙坦组20mg·kg-1·d-1ig+培垛普利组2mg·kg-1·d-1ig),术后次周起干预8周,观察左室重量指数(LVMI)和心肌细胞横径(TDM),免疫组织化学检测心肌CX43、结蛋白与cTnT表达。结果:培垛普利组、伊贝沙坦组和联合用药组LVMI和TDM均显著低于手术组(P<0·05),手术组心肌细胞闰盘区域和侧侧连接的胞膜上均有不规则CX43表达;伊贝沙坦组、培垛普利和其联用组的CX43表达分布较有规律,主要以带状表达于闰盘;手术组心肌CX43、结蛋白、cTnT表达量明显少于伊贝沙坦组、培垛普利组和其联用组(P<0·05)。结论:左室肥大时伊贝沙坦和培垛普利有利于心肌CX43、结蛋白与cTnT的表达与分布,能减轻左室心肌肥大,减少心肌细胞损伤,促进心肌细胞骨架结构与缝隙连接的基本正常恢复。

AIM： To investigate the effects of angiotensin Ⅱ receptor type Ⅰ antagonist irbesartan and angiotensin converting enzyme inhibitor perindopril on the myocardial expression of connexin 43 （CX43）, desmin and cardiac troponin T （cTnT） in the pressure, overload- induced rat cardiac hypertrophy. METHODS： 40 male adult Sprague- Dawley rats were divided into 5 groups （8 animals for each） ： sham operation group and other four groups with ventricular hypertrophy caused by banding aortic artery. Drugs were given one week after operation as follows： sham operation group, normal saline （2 mL·kg^-1·d^-1 ig） was given;Operative groups： animals with ventricular hypertrophy were treated with normal saline 2mL·kg^-1· d^-1 ig; Treatment groups： animals with ventricular hypertrophy were treated with perindopril 2 mg·kg^-1·d^-1 ig, irbesartan 20 mg·kg^-1·d^-1 ig or irbesartan 20mg·kg^-1·d^-1 ig plus perindopril 2 mg·kg^-1·d^-1 ig, respectively. Left ventricular mass index （LVMI）, transverse diameter of myocardial cell （TDM）, and myocardial expression of CX43, desmin and cTnT by immunohistochemistry were performed at the end of 8 weeks of drug intervention. RESULTS： LVMI, TDM were remarkably decreased after drug intervention, compared to animals of operative group （ P 〈 0.05）. Left ventricular hypertrophy induced by aortic banding in rots were associated with marked disorganization of gap junction distribution. In hypertrophied myocytes, CX43 immunolabeling was dispersed over the entire cell surface rather than confined to the intercalated disks. The CX43 were mainly distributed in the interealated disks in irbesartan group,perindopril group and their combined group. The myocardial expression of CX43, desmin and cTnT in the operative group was lower Ihan that in irlyesanan group, perindopril group and their combined group （P 〈 0.05 ）, CONCLUSION： These data indicate that irbesartan and perindopril play beneficial roles in the myocardial CX43, desmin and cTnT expression and their distribution, and the restoratiou of myocardial cell structure and gap junclion in pressure - overload myoeardium hypertrophy.